Gibbs states over the cone of discrete measures

We construct Gibbs perturbations of the Gamma process on \mathbbm{R}^d, which may be used in applications to model systems of densely distributed particles. First we propose a definition of Gibbs measures over the cone of discrete Radon measures on \mathbbm{R}^d and then analyze conditions for their existence. Our approach works also for general L\'evy processes instead of Gamma measures. To this end, we need only the assumption that the first two moments of the involved L\'evy intensity measures are finite. Also uniform moment estimates for the Gibbs distributions are obtained, which are essential for the construction of related diffusions. Moreover, we prove a Mecke type characterization for the Gamma measures on the cone and an FKG inequality for them.Comment: Keywords: Gamma process, Poisson point process, discrete Radon measures, Gibbs states, DLR equation, Mecke identity, FK

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The monetary benefit of early flood warnings in Europe

Effective disaster risk management relies on science-based solutions to close the gap between prevention and preparedness measures. The consultation on the United Nations post-2015 framework for disaster risk reduction highlights the need for cross-border early warning systems to strengthen the preparedness phases of disaster risk management, in order to save lives and property and reduce the overall impact of severe events. Continental and global scale flood forecasting systems provide vital early flood warning information to national and international civil protection authorities, who can use this information to make decisions on how to prepare for upcoming floods. Here the potential monetary benefits of early flood warnings are estimated based on the forecasts of the continental-scale European Flood Awareness System (EFAS) using existing flood damage cost information and calculations of potential avoided flood damages. The benefits are of the order of 400 Euro for every 1 Euro invested. A sensitivity analysis is performed in order to test the uncertainty in the method and develop an envelope of potential monetary benefits of EFAS warnings. The results provide clear evidence that there is likely a substantial monetary benefit in this cross-border continental-scale flood early warning system. This supports the wider drive to implement early warning systems at the continental or global scale to improve our resilience to natural hazards

Correlating Global Gene Regulation to Angiogenesis in the Developing Chick Extra-Embryonic Vascular System

International audienceBACKGROUND: Formation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. Determining genes, which drive vascular maturation is crucial for the identification of new therapeutic targets against pathological angiogenesis. METHOLOGY/PRINCIPAL FINDINGS: We accessed global gene regulation throughout maturation of the chick chorio-allantoic membrane (CAM), a highly vascularized tissue, using pan genomic microarrays. Seven percent of analyzed genes showed a significant change in expression (>2-fold, FDR<5%) with a peak occurring from E7 to E10, when key morphogenetic and angiogenic genes such as BMP4, SMO, HOXA3, EPAS1 and FGFR2 were upregulated, reflecting the state of an activated endothelium. At later stages, a general decrease in gene expression occurs, including genes encoding mitotic factors or angiogenic mediators such as CYR61, EPAS1, MDK and MYC. We identified putative human orthologs for 77% of significantly regulated genes and determined endothelial cell enrichment for 20% of the orthologs in silico. Vascular expression of several genes including ENC1, FSTL1, JAM2, LDB2, LIMS1, PARVB, PDE3A, PRCP, PTRF and ST6GAL1 was demonstrated by in situ hybridization. Up to 9% of the CAM genes were also overexpressed in human organs with related functions, such as placenta and lung or the thyroid. 21-66% of CAM genes enriched in endothelial cells were deregulated in several human cancer types (P<.0001). Interfering with PARVB (encoding parvin, beta) function profoundly changed human endothelial cell shape, motility and tubulogenesis, suggesting an important role of this gene in the angiogenic process. CONCLUSIONS/SIGNIFICANCE: Our study underlines the complexity of gene regulation in a highly vascularized organ during development. We identified a restricted number of novel genes enriched in the endothelium of different species and tissues, which may play crucial roles in normal and pathological angiogenesis

Evaluating Simulations as Preparation for Health Crises like CoVID-19: Insights on Incorporating Simulation Exercises for Effective Response.

Today's health emergencies are increasingly complex due to factors such as globalization, urbanization and increased connectivity where people, goods and potential vectors of disease are constantly on the move. These factors amplify the threats to our health from infectious hazards, natural disasters, armed conflicts and other emergencies wherever they may occur. The current CoVID-19 pandemic has provided a clear demonstration of the fact that our ability to detect and predict the initial emergence of a novel human pathogen (for example, the spill-over of a virus from its animal reservoir to a human host), and our capacity to forecast the spread and transmission the pathogen in human society remains limited. Improving ways in which we prepare will enable a more rapid and effective response and enable proactive preparations (including exercising) to respond to any novel emerging infectious disease outbreaks. This study aims to explore the current state of pandemic preparedness exercising and provides an assessment of a number of case study exercises for health hazards against the key components of the WHO's Exercises for Pandemic Prepared Plans (EPPP) framework in order to gauge their usefulness in preparation for pandemics. The paper also examines past crises involving large-scale epidemics and pandemics and whether simulations took place to test health security capacities either in advance of the crisis based on risk assessments, strategy and plans or after the crisis in order to be better prepared should a similar scenario arise in the future. Exercises for animal and human diseases have been included to provide a "one health" perspective [1,2]. This article then goes on to examine approaches to simulation exercises relevant to prepare for health crisis involving a novel emergent pathogen like CoVID-19. This article demonstrates that while simulations are useful as part of a preparedness strategy, the key is to ensure that lessons from these simulations are learned and the associated changes made as soon as possible following any simulation in order to ensure that simulations are effective in bringing about changes in practice that will improve pandemic preparedness. Furthermore, Artificial Intelligence (AI) technologies could also be applied in preparing communities for outbreak detection, surveillance and containment, and be a useful tool for providing immersive environments for simulation exercises for pandemic preparedness and associated interventions which may be particularly useful at the strategic level. This article contributes to the limited literature in pandemic preparedness simulation exercising to deal with novel health crises, like CoVID-19. The analysis has also identified potential areas for further research or work on pandemic preparedness exercising